Aim To investigate the association between paraoxonase-2 gene 311 Cys/Ser polymorphism and macrovascular disease in combination with paraoxonase-1 gene 192 Gln/Arg polymorphism in type 2 diabetes mellitus patients. Methods A case-control study of 272 Chinese subjects was performed.Genomic DNA was extracted from the subjects' peripheral blood leukocytes.The paraoxonase-1 gene 192 Gln/Arg and paraoxonase-2 gene 311 Cys/Ser polymorphisms were determined by PCR analysis.In addition,the association was investigated between paraoxonase-2 gene 311 Cys/Ser polymorphism and macrovascular disease in combination with paraoxonase-1 gene 192 Gln/Arg polymorphism in control group and type 2 diabetes mellitus complicated with macrovascular disease group. Results Paraoxonase-1 gene 192 Gln/Arg and paraoxonase-2 gene 311 Cys/Ser polymorphisms were detected in population of Qingdao.The genetype distribution(QQ,QR and RR) of paraoxonase-1 gene 192 Gln/Arg polymorphism showed no significant differences between type 2 diabetes mellitus complicated with macrovascular disease group and the other two groups(type 2 diabetes mellitus group & healthy subjects).But the genetype distribution(CC,CS and SS) of paraoxonase-2 gene 311 Cys/Ser polymorphism showed significant differences between type 2 diabetes mellitus complicated with macrovascular disease group and the other two groups,the former had a significantly higher S allele frequency(p<0.05 or p<0.01).The linkage analysis of paraoxonase2 gene 311 Cys/Ser and paraoxonase-1 gene 192 Gln/Arg gene polymorphisms further emphasized that paraoxonase-2 gene 311 S allele was an independent risk factor leading to type 2 diabetes mellitus complicated with macrovascular disease.When both of the paraoxonase-2 gene 311 S allele and the paraoxonase-1 gene 192 R allele existed,the OR of paraoxonase-2 gene 311 S allele for type 2 diabetes mellitus complicated with macrovascular disease was significantly higher(Or=49.494,95%CI: 0.907～2 701.872). Conclusions The paraoxonase-2 gene 311 Cys/Ser polymor-phism is associated with type 2 diabetes mellitus complicated with macrovascular disease in Qingdao's population.S allele may be a risk factor for type 2 diabetes mellitus complicated with macrovascular disease.Meanwhile,detecting the paraoxonase-1 gene 192 R allele may provide a more precise method to predict or diagnose type 2 diabetes mellitus complicated with macrovascular disease.